JP2016519930A5 - - Google Patents

Claims (29)

  An organoid containing a heterogeneous renal cell group and a biologically active cell group, wherein the heterogeneous renal cell group is enriched with a specific bioactive component or cell type and / or a specific inactive or undesirable Organoids wherein a component or cell type is depleted and the biologically active cell population comprises endothelial cells, endothelial progenitor cells, mesenchymal stem cells, and / or adipose derived progenitor cells.   The organoid according to claim 1, wherein the biologically active cell group is an endothelial cell group.   3. The heterogeneous renal cell group comprises a B2 cell group containing an enriched group of tubular cells, and wherein the heterogeneous renal cell group is depleted of the B1 cell group. Organoid.   4. The organoid of claim 3, wherein the heterogeneous renal cell group is further depleted of the B5 cell group.   The heterogeneous renal cell group contains a cell group selected from B2 / B3, B2 / B4, and B2 / B3 / B4, or contains erythropoietin (EPO) -producing cells. Organoid.   3. The organoid of claim 2, wherein the endothelial cell group is a cell line or comprises human umbilical vein endothelial cells (HUVEC).   A method for forming an organoid comprising a heterogeneous renal cell group and a biologically active cell group, wherein the heterogeneous renal cell group and the biologically active cell group are subjected to i) 2D culture; ii) 3D culture: collagen type I ( COL (I)) gel; iii) 3D culture: Matrigel; iv) 3D culture: spinner, then COL (I) / Matrigel; and v) 3D culture: collagen type IV (COL (IV)) gel Culturing in a culture system selected from the group, wherein the heterogeneous renal cell group is enriched with a specific bioactive component or cell type and / or a specific inactive or undesirable component or cell A method wherein the type-depleted and biologically active cell population comprises endothelial cells, endothelial progenitor cells, mesenchymal stem cells, and / or adipose-derived progenitor cells.   The heterogeneous renal cell group contains (i) a B2 cell group containing an enriched group of tubular cells, and wherein the heterogeneous renal cell group is depleted of the B1 cell group, (ii) 8. The method of claim 7, comprising a group of cells selected from B2, B2 / B3, B2 / B4, and B2 / B3 / B4, or (iii) containing erythropoietin (EPO) producing cells.   9. The method of claim 8, wherein the heterogeneous renal cell group is further depleted of the B5 cell group.   The method according to claim 7, wherein the biologically active cell group is an endothelial cell group.   The method according to claim 10, wherein the endothelial cell group is a cell line or contains HUVEC cells.   8. The method of claim 7, wherein the cell population is selected from a heterogeneous, syngeneic, allogeneic, self, and combinations thereof.   8. The method of claim 7, wherein the heterogeneous renal cell group and the biologically active cell group are cultured separately during the first period, mixed and cultured during the second period.   14. The method of claim 13, wherein the second period is at least 24 hours, or from 24 hours to 72 hours.   8. The method of claim 7, wherein the renal cell population and the biologically active cell population are in a 1: 1 ratio or suspended in a growth medium.   An organoid made according to the method of any one of claims 7 to 15.   An injectable preparation comprising at least one organoid according to any one of claims 1 to 6 and a liquid medium.   18. The formulation of claim 17, wherein the liquid medium is selected from cell growth medium, Dulbecco's phosphate buffered saline (DPBS), and combinations thereof.   The formulation according to claim 17, wherein the organoid is suspended in a liquid medium. The organoid according to any one of claims 1 to 6, and
(I) a substantially solid state at about 8 ° C. or less, and
(Ii) substantially in a liquid state above ambient temperature,
An injectable formulation comprising a temperature sensitive cell stabilized biomaterial that maintains a temperature.   (I) the bioactive cells are substantially uniformly distributed throughout the volume of the cell-stabilized biomaterial; (ii) the biomaterial is a solid-liquid at about 8 ° C. to about ambient temperature or above. 21. The formulation of claim 20, wherein (iii) the substantially solid state is a gel state, and (iv) the cell-stabilized biomaterial comprises a hydrogel.   The formulation according to claim 21, wherein the hydrogel comprises gelatin.   23. The formulation of claim 22, wherein gelatin is present in the formulation at about 0.5% to about 1% (w / v) or at about 0.75% (w / v).   An organoid for treating renal disease in a subject in need, comprising the organoid of any one of claims 1 to 6, wherein at least one said organoid is administered.   24. An injectable formulation for treating renal disease in a subject in need, comprising the formulation of any one of claims 20-23.   26. The organoid of claim 24 or the injectable formulation of claim 25, wherein the subject is a mammal.   27. The organoid or injectable formulation of claim 26, wherein the mammal is a human.   27. The organoid or injectable formulation of claim 26, wherein the subject has renal disease. 26. The organoid of claim 24 or the injectable formulation of claim 25, wherein an improvement in any one of the following criteria is observed:
Anemia (Hct, Hgb, RBC), inflammation (WBC), urine concentration (spGrav) and hypernitrogenemia (BUN).